Hirudin has an unusual asymmetry of structural elements. A compact, hydrophobic core region in the amino-terminal half of the molecule contains alternating polar and nonpolar segments and all three disulfide bonds. The carboxy-terminal region is more extended and extremely hydrophilic. The tight and essentially irreversible binding of hirudin to thrombin depends on both ionic and hydrophobic interactions.
In thrombotic disorders Hirudin inactivates thrombin by forming a 1:1 stoichiometric complex that is stable throughout the physiological pH range. Hirudin directly inhibits the active site pocket and the fibrinogen binding site of free and clot-bound thrombin.